Engineering Defects and Disorder for Enhanced Pharmaceutical Properties. Is there an order to disorder?

Defect control of solids is underexploited for molecular systems, but they can affect physical properties including hygroscopicity, dissolution rate, solubility, chemical stability, compressibility and formulation behavior.1 Study of disordered pharmaceuticals is highly relevant in understanding pharmaceutical processes and developing these in a sustainable context, improving understanding of API properties and manufacturability issues related to disorder. Multiple APIs form disordered crystals in development and commercial portfolios; their characterisation is vital, but this work looks beyond characterisation to control – can we use additive and related approaches to control defect and disorder formation (and hence solid-state properties) during crystallisation? Existing research in this area has focused on approaches to control amorphous materials and ignored the prospects of organic crystalline materials with small deviations in long range order.
 
Aim: In this study a pharmaceutically relevant model system that exhibits disorder, salbutamol sulfate (SAS), was used to show if disorder could be controlled by crystallisation and to establish a methodology suitable for the application of pharmaceutical compounds . The achievement of such a high level of control in solid state crystallisation, would be a step towards the creation of a new chemical technology; the control of disorder to tune the physical properties of crystalline molecular materials.